Diabetes mellitus is a serious and chronic metabolic disease that is characterized by high blood glucose (hyperglycemia) and affects millions of people world-wide. SGLT2 is a Sodium-dependent GLucose co-Transporter protein which affects the reabsorption of glucose in the kidney. It is estimated that 90% of renal glucose reabsorption is facilitated by SGLT2. Since glucose reabsorption is mediated predominantly by SGLT2 and because high glucose levels have been identified as a cause of disease in diabetes, SGLT2 has become a drug target for type 2 diabetes therapy. Selective inhibition of SGLT2 has the potential to reduce hyperglycemia by inhibiting glucose reabsorption in the kidney with elimination of glucose by excretion in the urine (glucosuria).
A significant number of SGLT2 inhibitors are currently in clinical development and a significant portion of these are β-C-arylglucosides. Further, a series of therapeutically effective β-C-glucosides (i.e., canagliflozin, dapagliflozin, ipragliflozin and empagliflozin) that are Sodium-coupled GLucose co-Transporter 2 (SGLT2) inhibitors have recently received marketing approval for the treatment of diabetes mellitus.
Among the β-C-arylglucosides as SGLT2 inhibitors, it is noted that dapagliflozin and empagliflozin share the same core structure and differ only in the O-substitution of terminal phenoxy group, which makes both feasible to manufacture in single synthetic route(s).

Dapagliflozin (trade name Farxiga) was developed by Bristol-Myers Squibb in partnership with AstraZeneca. The FDA approved dapagliflozin for glycemic control, along with diet and exercise, in adults with type 2 diabetes on Jan. 8, 2014. Dapagliflozin is chemically named as (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol.
Empagliflozin (trade name Jardiance) was developed by Boehringer Ingelheim and Eli Lilly and Company, and approved for the treatment of type 2 diabetes in adults in 2014. Empagliflozin is chemically named as (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol. Both empagliflozin and dapagliflozin are inhibitors of the sodium glucose co-transporter-2 (SGLT-2), which causes sugar in the blood to be excreted by the kidneys and eliminated in urine.
A series of synthetic methods have been reported in the literature that can be used for the preparation of dapagliflozin and empagliflozin. For example, U.S. Pat. No. 6,414,126, U.S. Pat. No. 6,515,117 and WO 2004/063209 disclose similar synthetic route and intermediates for preparing dapagliflozin. WO 2005/092877, WO 2006/120208, WO 2011/039108 and WO 2015/101916 disclose various approaches and intermediates for preparing empagliflozin.
There is a need for novel and efficient process for the preparation of β-C-arylglucosides. This invention addresses those needs.